FGF signaling in mammary gland fibroblasts regulates multiple fibroblast functions and mammary epithelial morphogenesis

SUMBAL, Jakub and Zuzana KOLEDOVÁ. FGF signaling in mammary gland fibroblasts regulates multiple fibroblast functions and mammary epithelial morphogenesis. Development. CAMBRIDGE: COMPANY BIOLOGISTS LTD, 2019, vol. 143, No 23, p. 1-16. ISSN 0950-1991. Available from: https://dx.doi.org/10.1242/dev.185306.

Basic information

• Original name: FGF signaling in mammary gland fibroblasts regulates multiple fibroblast functions and mammary epithelial morphogenesis
• Authors: SUMBAL, Jakub (203 Czech Republic, belonging to the institution) and Zuzana KOLEDOVÁ (703 Slovakia, guarantor, belonging to the institution).
• Edition: Development, CAMBRIDGE, COMPANY BIOLOGISTS LTD, 2019, 0950-1991.

Other information

• Original language: English
• Type of outcome: Article in a journal
• Field of Study: 10605 Developmental biology
• Country of publisher: United Kingdom of Great Britain and Northern Ireland
• Confidentiality degree: is not subject to a state or trade secret
• WWW: URL
• Impact factor: Impact factor: 5.611
• RIV identification code: RIV/00216224:14110/19:00108153
• Organization unit: Faculty of Medicine
• Doi: http://dx.doi.org/10.1242/dev.185306
• UT WoS: 000507575700017
• Keywords in English: Branching morphogenesis; Collagen; Extraceliular matrix; Fibroblast; Fibroblast growth factor; Mammary gland; Stroma; Mouse
• Tags: 14110517, CF CELLIM, rivok

Abstract

Fibroblast growth factor (FGF) signaling is crucial for mammary gland development. Although multiple roles for FGF signaling in the epithelium have been described, the function of FGF signaling in mammary stroma has not been elucidated. In this study, we investigated FGF signaling in mammary fibroblasts. We found that murine mammary fibroblasts express FGF receptors FGFR1 and FGFR2 and respond to FGF ligands. In particular, FGF2 and FGF9 induce sustained ERK1/2 signaling and promote fibroblast proliferation and migration in 2D cultures. Intriguingly, only FGF2 induces fibroblast migration in 3D extracellular matrix (ECM) through regulation of actomyosin cytoskeleton and promotes force-mediated collagen remodeling by mammary fibroblasts. Moreover, FGF2 regulates production of ECM proteins by mammary fibroblasts, including collagens, fibronectin, osteopontin and matrix metalloproteinases. Finally, using organotypic 3D co-cultures we show that FGF2 and FGF9 signaling in mammary fibroblasts enhances fibroblast-induced branching of mammary epithelium by modulating paracrine signaling, and that knockdown of Fgfr1 and Fgfr2 in mammary fibroblasts reduces branching of mammary epithelium. Our results demonstrate a pleiotropic role for FGF signaling in mammary fibroblasts, with implications for regulation of mammary stromal functions and epithelial branching morphogenesis.

Links

• GJ16-20031Y, research and development project: Name: Signalizace FGF ve fibroblastech mléčné žlázy a její úloha ve vývoji a nádorech mléčné žlázy

Investor: Czech Science Foundation

• MUNI/E/0519/2019, interní kód MU: Name: The role of fibroblasts and FGF signaling in mammary gland development: Upgrade and finalization of publication

Investor: Masaryk University, Promoting quality excellence

• ROZV/24/LF/2018, interní kód MU: Name: LF - Příspěvek na IP 2108

Investor: Ministry of Education, Youth and Sports of the CR, Internal development projects